Lymphoproliferative malignancies, including lymphomas and lymphocytic leukemia, are common malignancies with an incidence of approximately 93,000 new cases a year in the United States.
Treatment modalities being developed to treat these malignancies are being met with varying levels of success. For example, among the more than 30 subtypes of non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL) accounts for 3 percent to 10 percent of cases. MCL can be treated at diagnosis or recurrence with various chemotherapeutic regimens. Although the prognosis is improving given these advances in treatment, the median overall survival remains 4.8 years.
Follicular lymphoma (FL) is a common indolent B-cell NHL that constitutes approximately 20 percent of all newly diagnosed lymphoma cases and approximately 70 percent of all indolent NHL. Like many lymphomas, it is increasing in incidence, with over 24,000 new cases diagnosed each year. While there is an increasing number of available treatment modalities for FL, including radioimmunotherapy alone or in combination with chemotherapy, as well as bone marrow transplantation, many FL patients develop treatment-refractory disease or relapse due to molecular escape mechanisms.
B-cell chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the United States, with approximately 15,000 new cases each year. According to the World Health Organization (WHO) classification, CLL is identical (i.e., one disease at different stages) to the mature peripheral B-cell neoplasm small lymphocytic lymphoma (SLL). In spite of various treatment options, CLL/advanced SLL is a progressive disease and once symptomatic, patients have a relatively short overall survival, ranging from 18 months to 6 years, with a 22.5 percent 10-year survival expectation.
As a result, there is an ongoing need for clinically effective agents for treating lymphoproliferative malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, Hodgkin's lymphoma, Waldenstrom's macroglobulinemia, follicular lymphoma, or diffuse large B-cell lymphoma or transformed lymphoma.